Project Summary: Past experimental investigations have demonstrated that the application of HIFU (High Intensity Focused Ultrasound) to cancerous tumors results in the release of heat shock proteins and a beneficial immunizing effect. The release of proteins into the blood as a result of HIFU therapy is further demonstrated by the spike of the serum prostate specific antigen (PSA) level following HIFU treatment of the prostate. The goal of this proposal is to build on the HIFU treatment of local tumors in order to address metastases. We propose to use an immunotherapy approach to address metastatic disease following the application of HIFU for the treatment of local disease. The immunotherapy procedure amplifies the immunizing effect of the heat shock proteins. HIFU is an ideal approach for stimulating the immunizing effect since it is noninvasive and repeatable with the ability to precisely target tissue. The specific aims are 1) to build a HIFU delivery system that permits the user to control the power, frequency, pulse length, and pulse repetition frequency, 2) to create an ultrasonic probe to interface with the HIFU delivery system and be scaled to work with a small animal model, and 3) to use the HIFU delivery system and probe in a small animal model with immunotherapy. The animal model study will provide details on the effectiveness of the treatment and are needed to determine the preferred parameters for both HIFU and immunotherapy. In phase II, the method will be implemented in the Sonablate(r) 500 prostate cancer system and a series of large animal studies will be performed to lay the foundation for human clinical trials. The method of applying HIFU therapy in conjunction with immunotherapy has the potential to expand the market for the Sonablate(r) 500 system from the current indication of organ confined prostate cancer to include advanced stage prostate cancer with evidence of metastasis or a high risk of metastasis. Relevance: In 2004, an estimated 230,000 men were diagnosed with prostate cancer and 30,000 died of prostate cancer in the U.S.. There exists a number of approaches to treat organ confined prostate cancer of which HIFU is an example. To expand on the success of treating the local disease, the goal of this project is to address metastatic disease through the combination of HIFU treatment of prostate cancer followed by immunotherapy (method for boosting the immune response of the body). [unreadable] [unreadable] [unreadable]